Axon loss and neurodegeneration constitute clinically debilitating sequelae in demyelinating diseases such as multiple sclerosis, but the underlying mechanisms of secondary degeneration are not well understood. Myelinating glia play a fundamental role in promoting the maturation of the axon cytoskeleton, regulating axon trafficking parameters, and imposing architectural rearrangements such as the nodes of Ranvier and their associated molecular domains. In the setting of demyelination, these changes may be reversed or persist as maladaptive features, leading to axon degeneration. In this review, we consider recent insights into axon-glial interactions during development and disease to propose that disruption of the cytoskeleton, nodal architecture, and other components of axon infrastructure is a potential mediator of pathophysiological damage after demyelination.

Chapter 1. The first chapter discusses the background of peptides and their potential as drugs. The methodologies for peptide synthesis via solution and solid-phase as well as macrocyclization strategies for cyclic peptides. Cyclic peptides' biological activity and the challenges for peptide drug development. Chapter 2. This chapter emphasizes on the design, synthesis and Structural Activity Relationship (SAR) of San A derivatives. Six novel San A derivatives were designed based on the structural features of developed potent San A derivatives. The structural modifications of novel San A derivatives included : 1) D-amino acid incorporation, 2) insertion of N-Me-amino acid, and 3) Aliphatic size chain reduction. The cytotoxicity of synthesized San A derivatives were exanimated against pancreatic cancer cell line PL-45 using 3H-Thymidine incorporation assay. The biological results and SAR studies of six novel San A derivatives were discussed in this chapter. Chapter 3. Histone deacetylase (HDACs) are a class of enyzmes that are responsible for regulating the acetylation state of the histones. In many cancers, overexpression of HDACs is observed resulting hypoacetylation state of histones and improper gene transcriptions, which leads to tumor progression. Thus, the development of novel HDIs is critical for combating cancers. Chapter 3 focuses on the design and synthesis of novel Histone Deacetylase Inhibitors (HDIs) based on two cyclic tetrapeptide natural products: FR235222 and trapoxin B. The biological test results of developed novel HDIs and the discussion of structure-activity relationship are also presented. Chapter 4. Urukthepelstatin A (Ustat A) is a macrocyclic compound, which composed of a heterocyclic backbone and a peptide segment. Ustat A exhibits potent anti-tumor activity (GI₅₀ = 15.5 nM) and its biological mechanism varies from other structurally similar scaffolds. Thus, the development of Ustat A provides an opportunity to explore a novel cell-survival pathway. In chapter 4, a convergent synthetic approach for Ustat A and its derivatives was described. Ustat A derivatives were designed based on heterocycle placement strategy, which was never reported in literature. In this chapter, the synthesis of linear precursor and the cyclization attempt for Ustat A derivative Ustat A-2 were presented

Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated-Hubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p = 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulation-public health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.

A case study of catalytic carbon-carbon σ-bond homolysis is presented. The coordination of a redox-active Lewis acid catalyst reduces the bond-dissociation free energies of adjacent carbon-carbon σ-bonds, and this complexation-induced bond-weakening is used to effect reversible carbon-carbon bond homolysis. Stereochemical isomerization of 1,2-disubstituted cyclopropanes was investigated as a model reaction with a ruthenium (III/II) redox couple adopted for bond weakening. Results from our mechanistic investigation into the stereospecificity of the isomerization reaction are consistent with selective complexation-induced carbon-carbon bond homolysis. The ΔG‡ of catalyzed and uncatalyzed reactions were estimated to be 14.4 and 40.0 kcal/mol, respectively with the computational method, (U)PBE0-D3/def2-TZVPP-SMD(toluene)//(U)B3LYP-D3/def2-SVP. We report this work as the first catalytic example where the complexation-induced bond-weakening effect is quantified through transition state analysis.

Herder’s ideas on cultural plurality in language offer an explanation for how narrative might bridge cultural boundaries. In his Essay on the Origin of Language Herder focuses on language as the specifically human trait that distinguishes humanity from all other species on the one hand and the creator of human differences and diversity of cultures on the other hand. The crucial issue for Herder’s aesthetics of language is the reception process whereby a particular experience acquires linguistic form. This process functions in the origin of language and in the translation from one language to another in a similar way. In both cases, the particular environmental forces that are significant in the mind of the receiver become crucial for the shaping of the final linguistic or narrative construct being received. If this is true, then cases of transcultural narrative are not examples of the creation of a ‘common’ narrative. Rather, narrative ‘proliferates’ across cultures by multiplying itself in a process that is determined by a certain confluence of interests in two or more cultures but not a reproduction of identical narrative forms, even in the case of direct translation. © 2004 Taylor and Francis Group, LLC.

Botho Strauss's (1993) attempts to resurrect a premodern approach to German culture centered on themes such as the sacred & myth is defended against those who see it as a resurgence of Nazi themes. This attempt to reintroduce the power of a traditional religion-based culture is based on three claims about culture: (1) A crisis of values is inevitable for a society organized around economic prosperity. (2) Tradition-based authority is essential for the building of individuals. (3) Violence against scapegoats is necessary for the maintenance of social order. The idea of the sacred & its relation to myth, imagination, & the sublime are made central to political organization. On all these issues, Strauss is invoked as an alternative to the standard liberal positions derived from Immanuel Kant. Strauss is criticized for privileging German language over concrete interpersonal relations, which serves to render his notions of sacred & community into a contrived nationalism that removes art from the everyday. A reading of Strauss's works provides an example of how myth can provide meaning to recent German history. H. von Rautenfeld

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.